ST-segment resolution 60 minutes after combination treatment of abciximab with reteplase or reteplase alone for acute myocardial infarction (30-day mortality results from the resolution of ST-segment after reperfusion therapy substudy)

doi:10.1016/j.amjcard.2004.06.018

The American Journal of Cardiology

Volume 94, Issue 7, 1 October 2004, Pages 859-863

https://doi.org/10.1016/j.amjcard.2004.06.018 Get rights and content

The combination of abciximab with thrombolytic therapy when treating acute ST-elevation myocardial infarction has been hypothesized to enhance microvascular perfusion. Resolution of ST-segment elevation after thrombolytic therapy is believed to be a marker of myocardial reperfusion and to predict mortality rate. Among 16,588 patients enrolled in the Fifth Global Use of Strategies to Open Occluded Arteries in Acute Myocardial Infarction trial, 1,764 consecutive patients from selected centers had their study electrocardiograms evaluated by a core laboratory for ST-segment deviation resolution 60 minutes after treatment. Patients were categorized into 4 groups: complete resolution (>70%), partial resolution (<70% to 30%), no resolution (<30%), and worsening ST-segment deviation. Patients treated with reteplase or a combination of reteplase plus abciximab had similar rates of complete resolution (32% vs 34%), partial resolution (29% vs 27%), no resolution (15% vs 16%), and worsening ST-segment elevation (23 vs 23%; p = 0.59). The 30-day mortality rates in these 4 groups were 2.1%, 5.2%, 5.5%, and 8.1% (p <0.001). Even after accounting for baseline variables, incomplete ST-segment resolution (<70%) was associated with an increased risk of death within 30 days (adjusted hazard ratio 2.41, 95% confidence interval 1.25 to 4.63, p <0.008). Thus, ST-segment resolution at 60 minutes was no different in patients treated with full-dose reteplase from those treated with a combination of abciximab and reteplase. Patients with >70% ST-segment resolution within 60 minutes had markedly decreased mortality rates, irrespective of treatment.

Section snippets

Study population

The Fifth Global Use of Strategies to Open Occluded Arteries in Acute Myocardial Infarction (GUSTO V) trial¹ included patients who had continuous symptoms of chest discomfort of 30 minutes to 6 hours and ST-elevation consistent with AMI or presumed new left bundle branch block. Exclusion criteria included age <18 years old, planned catheter-based reperfusion, active bleeding or a noncompressible vascular puncture site, systolic blood pressure >180 mm Hg or diastolic pressure >110 mm Hg, use of

Study population

Of 16,588 patients enrolled in the GUSTO V trial, 2,066 consecutive patients were identified as potentially eligible for the RESTART substudy. A total of 302 patients (14%) was excluded due to left bundle branch block (n = 72, 3.5%), previous pacemaker placement (n = 6, 0.3%), sustained ventricular tachycardia or fibrillation (n = 41, 2.0%), absence of ST-segment elevation on the baseline ECG (n = 74, 3.6%), or a technically inadequate ECG (n = 107, 5.2%), leaving 1,764 analyzed patients. The

Discussion

We found that a combination of half-dose reteplase and usual-dose abciximab among patients who had AMI was associated with a similar extent of resolution of ST-segment deviation compared with standard-dose reteplase therapy alone. We also found a potentially powerful role of early electrocardiographic measurement of the resolution of ST-segment deviation as soon as 60 minutes after reperfusion therapy for prediction of mortality within 30 days.

Fibrinolytic treatment for ST-elevation AMI is

(16)

R. Schroder et al.
Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction
J Am Coll Cardiol
(1994)
R. Schroder et al.
Extent of early ST segment elevation resolution: a strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimensA substudy of the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial
J Am Coll Cardiol
(1995)
L. Pilote et al.
Recurrent ischemia after thrombolysis for acute myocardial infarction
Am Heart J
(2001)
J.A. de Lemos
ST-segment resolution as a marker of epicardial and myocardial reperfusion after thrombolysis: insights from the TIMI 14 and in TIME-II trials
J Electrocardiol
(2000)
G.M. Santoro et al.
Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated with direct angioplasty
Am J Cardiol
(1998)
J.A. de Lemos et al.
ST-segment resolution and infarct-related artery patency and flow after thrombolytic therapyThrombolysis In Myocardial Infarction (TIMI) 14 investigators
Am J Cardiol
(2000)
A.W. van 't Hof et al.
Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarctionZwolle Myocardial Infarction Study Group
Lancet
(1997)
E.J. Topol
Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial
Lancet
(2001)

There are more references available in the full text version of this article.

Cited by (22)

Effect of prolonged bivalirudin infusion on ST-segment resolution following primary percutaneous coronary intervention (from the PROBI VIRI 2 Study)
2011, American Journal of Cardiology
Citation Excerpt :
This study was not powered for hard clinical end points. In this study we have shown that prolonged infusion of bivalirudin is associated with early tissue reperfusion comparable to that achieved with abciximab, which was shown previously to improve this parameter after primary PCI.6 Moreover, the 4-hour prolonged infusion demonstrated improved ST-segment recovery compared to standard bivalirudin treatment.
Bivalirudin is widely used as an anticoagulant during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction. However, an increase in acute stent thrombosis rates has been found in the HORIZONS-AMI trial. A prolonged infusion after PCI has been shown to be a safe and effective tool in patients undergoing urgent or elective PCI in the PROBI VIRI study. We examined the effects of prolonged drug infusion after primary PCI. From databases of 5 high-volume centers we compared a group of patients treated with a 4-hour prolonged infusion after PCI to 2 groups treated with a peri-PCI infusion and heparin plus abciximab. The primary study end point was >70% ST-segment resolution within 90 minutes after PCI; secondary end points were partial (>50%) ST-segment resolution within 90 minutes and intrahospital major and minor bleedings on the Acuity scale. The study population consisted of 264 patients undergoing primary PCI who were pretreated with aspirin and clopidogrel. The 3 study groups did not differ significantly by baseline characteristics. The primary end point was achieved in 69.8%, 48.8%, and 69.6% of patients in the prolonged bivalirudin, bivalirudin, and heparin/abciximab groups, respectively (p = 0.048 for prolonged vs standard infusion, p = 0.98 for prolonged infusion vs abciximab). Major bleedings and other secondary study end points were not significantly different among study groups. In conclusion, a strategy of prolonged bivalirudin infusion after primary PCI seems equivalent to a strategy with heparin plus abciximab, with an improvement in standard infusion in obtaining early microvascular reperfusion.
Does ST resolution achieved via different reperfusion strategies (fibrinolysis vs percutaneous coronary intervention) have different prognostic meaning in ST-elevation myocardial infarction? A systematic review
2010, American Heart Journal
Citation Excerpt :
Figure 1 shows the meta-analysis search results, the study selection process, and the reasons for exclusion. Table I (online Appendix) shows the 22 included papers3,9,12-31 (17 fibrinolysis studies including 31,710 patients, 4 PCI studies including 1,311 patients, and 1 comparative study9 between fibrinolysis and PCI with 1,233 patients randomized), thus giving 18 fibrinolysis cohorts (32,341 patients) and 5 PCI cohorts (1,913 patients). We use ST-resolution data by summation of infarct leads in all cohorts.
We perform a systematic review to discern if ST resolution achieved via percutaneous coronary intervention (PCI) has a different meaning to that achieved via fibrinolysis.
Resolution of ST-segment elevation in acute myocardial infarction has been widely used as a surrogate for treatment success. A recent randomized study suggested that after primary PCI, the prognostic significance of ST resolution may have been overemphasized.
Using the MEDLINE, COCHRANE, EMBASE, and PUBMED databases to search for the relevant papers, we analyze the data with a new ST-resolution score. ST-resolution groups of <30%, 30% to <70%, and ≥70% are given scores of 1, 2, and 3 respectively, whereas ST-resolution groups reported as <50% are scored as 1.5, and ≥50% scored as 2.5.
We identify 18 fibrinolysis cohorts (32,341 patients) and 5 PCI cohorts (1,913 patients). The mean ST-resolution score weighted for the number of patients in each cohort is 1.87 ± 0.15 for PCI and 1.66 ± 0.20 for fibrinolysis (P < .001). The raw combined 30-day mortality is 4.9% with fibrinolysis and 4.3% with PCI (P = .452 by Poisson regression). There is a linear relationship with lower 30-day mortality associated with higher ST-resolution score. The regression line for the PCI cohorts almost overlaps with that from the fibrinolysis cohorts. On multivariate regression, only ST-resolution score is significant in predicting 30-day mortality. When tested, the interaction term (treatment group × ST resolution score) is never a significant predictor (P > .25 in all models).
ST resolution after different reperfusion therapies has similar prognostic meaning.
ST-segment resolution assessed immediately after primary percutaneous coronary intervention correlates with infarct size and left ventricular function in cardiac magnetic resonance at 1-year follow-up
2009, Journal of Electrocardiology
Citation Excerpt :
For modern lytics, ECG after 60 and 90 minutes is usually used. For streptokinase, longer time up to 120 minutes is allowed.7-11 The value of ST-segment assessment after mechanical reperfusion was also studied extensively.
Little is known about the predictive value of electrocardiographic ST-segment resolution (STR) assessed immediately after primary percutaneous coronary intervention (PCI). The aim of the study was to analyze the value of STR and maximum single-lead ST-segment elevation assessed immediately after primary PCI in prediction of infarct size and left ventricular function in cardiac magnetic resonance (CMR) at 1-year follow-up.
A total of 28 patients with anterior wall ST-segment elevation myocardial infarction treated with primary PCI entered the study. There was a significant correlation of STR and maximum single-lead ST-segment elevation assessed immediately after primary PCI and CMR infarct size and left ventricular function after 1 year. When analyzed according to standard optimal reperfusion cutoff (70% for STR and 1 mm for single-lead elevation), both electrocardiographic parameters were also good predictors of CMR infarct size and left ventricular function after 1 year.
ST-segment resolution and the single-lead maximum ST-segment elevation assessed immediately after primary PCI for ST-segment elevation myocardial infarction are good predictors of infarct size and left ventricular function in 1-year follow-up.
Contrast echocardiography accurately predicts myocardial perfusion before angiography during acute myocardial infarction
2007, Canadian Journal of Cardiology
: To determine whether myocardial contrast echocardiography (MCE) can quickly and accurately assess myocardial perfusion and infarct-related artery (IRA) patency before emergency angiography during acute myocardial infarction (AMI).
Despite encouraging experimental and clinical studies, the reliability and practicality of MCE in predicting IRA patency during AMI before angiography has not been proven.
Two-dimensional echocardiography and MCE were performed in 51 patients with AMI just before emergency angiography. With knowledge of the electrocardiogram findings and regional wall motion, myocardial perfusion was assessed to predict IRA patency.
Myocardial perfusion studies were adequate for interpretation in 40 patients. An occluded IRA was predicted in 28 patients; the artery was occluded in 22 patients, and six patients had Thrombolysis In Myocardial Infarction (TIMI) grade 2 flow or less. A patent IRA was predicted in 12 patients; eight patients had TIMI grade 3 flow, one patient had TIMI grade 2 flow and the IRA was occluded in three patients. In one of the three patients, the appropriate view was not obtained. In another patient, collateral flow was adequate for near-normal regional wall motion, and in the last, the findings suggested reperfusion of the proximal artery with distal embolic occlusion. Taken together, MCE accurately predicted either TIMI grade 2 flow or less, or TIMI grade 3 flow in 36 of 40 patients. Sensitivity was 87.5%, specificity and positive predictive value were 100% and negative predictive power was 66.7% (P < 0.001).
MCE, together with the electrocardiogram and regional wall motion, can be used to quickly and reliably predict IRA patency early during AMI and may be useful to facilitate a management strategy.
Déterminer si l’échocardiographie myocardique de contraste (ÉMC) peut évaluer avec rapidité et précision la perfusion myocardique et la perméabilité de l’artère reliée à l’infarctus (ARI) avant l’angiographie d’urgence pendant un infarctus aigu du myocarde (IAM).
Malgré des études expérimentales et cliniques encourageantes, on n’a pas encore démontré la fiabilité et la valeur concrète de l’ÉMC à prédire la perméabilité de l’ARI pendant l’IAM avant l’angiographie.
On a procédé à une échocardiographie bidimensionnelle et à une ÉMC chez 51 patients atteints d’un IAM juste avant qu’ils subissent une angiographie d’urgence. Compte tenu des résultats de l’électrocardiogramme et du mouvement régional de la paroi, les auteurs ont évalué la perfusion myocardique pour prédire la perméabilité de l’ARI.
Les études de perfusion myocardique ont permis l’interprétation chez 40 patients. On a prédit une occlusion de l’ARI chez 28 patients. Cette occlusion a été vérifiée chez 22 patients, et six patients ont eu une thrombolyse dans l’infarctus du myocarde (TIMI) avec débit de grade 2 ou moins. On a prédit une ARI perméable chez 12 patients. Huit patients ont subi une TIMI avec débit de grade 3, un patient a subi une TIMI avec débit de grade 2, et on a constaté une occlusion de l’ARI chez trois patients. Chez l’un des trois patients, on n’a pu obtenir la vue pertinente. Chez un autre patient, le débit collatéral assurait un mouvement quasinormal de la paroi, et chez le dernier, les résultats laissaient supposer une reperfusion de l’artère proximale avec occlusion embolique distale. Dans l’ensemble, l’ÉMC permet de prédire avec précision la TIMI avec débit de grade 2 ou moins ou la TIMI avec débit de grade 3 chez 36 des 40 patients. La sensibilité s’élevait à 87,5%, la spécificité et la valeur prédictive positive, à 100%, et la puissance prédictive négative, à 66,7% (p < 0,001).
L’ÉMC, conjointement avec l’électrocardiogramme et le mouvement régional de la paroi, peut être utilisée pour prédire avec rapidité et précision la perméabilité de l’ARI au début de l’IAM et peut être utile pour faciliter une stratégie de prise en charge.
Protection of Distal Embolization in High-Risk Patients With Acute ST-Segment Elevation Myocardial Infarction (PREMIAR)
2007, American Journal of Cardiology
Citation Excerpt :
In brief, peak ST elevation before PCI was compared with ST-segment levels 60 minutes after the final contrast injection in the most abnormal single lead of the standard 12-lead electrocardiogram. Percent resolution of ST-segment elevation was categorized as complete (>70%), partial (30% to 70%), or absent (<30%).13 The primary end point of the study was the dichotomous rate of complete ST-segment resolution at 60 minutes, defined as ≥70% recovery compared with baseline during continuous ST-segment monitoring.
Distal embolization may decrease myocardial reperfusion after primary percutaneous coronary intervention (PCI). Nonetheless, results of previous trials assessing the role of distal protection during primary PCI have been controversial. The Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction Trial (PREMIAR) was a prospective, randomized, controlled study designed to evaluate the role of filter-based distal protection during PCI in patients with acute ST-segment elevation myocardial infarction at high risk of embolic events (including only baseline Thrombolysis In Myocardial Infarction grade 0 to 2 flow). The primary end point was continuous monitoring of ST-segment resolution. Secondary end points included core laboratory analysis of angiographic myocardial blush, ejection fraction measured by cardiac ultrasound, and adverse cardiac events at 6 months. From a total of 194 enrolled patients, 140 subjects were randomized to PCI with or without embolic protection, and 54 were included in a registry arm due to the presence of angiographic exclusion criteria. Baseline characteristics were comparable between arms. The rate of complete ST-segment resolution (≥70%) at 60 minutes was similar in patients treated with or without distal protection (61.2% vs 60.3%, respectively, p = 0.85). Angiographic myocardial blush (67% vs 70.7%, p = 0.73), in-hospital ejection fraction (47.4 ± 9.9% vs 45.3 ± 7.3%, p = 0.29), and combined end point of death, heart failure, or reinfarction at 6 months (14.3% vs 15.7%, p = 0.81) were consistently achieved in a similar proportion in the 2 groups. In conclusion, the use of filter-based distal protection is safe and effectively retrieves debris; however, such use does not translate into an improvement of myocardial reperfusion, left ventricular performance, or clinical outcomes.
Facilitated PCI in patients with ST-elevation myocardial infarction
2008, New England Journal of Medicine
We hypothesized that percutaneous coronary intervention (PCI) preceded by early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or with abciximab alone (abciximab-facilitated PCI) would improve outcomes in patients with acute ST-segment elevation myocardial infarction, as compared with abciximab administered immediately before the procedure (primary PCI).
In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximab-facilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization.
A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P=0.01 and P=0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P=0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P=0.49).
Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228.)
Immediate percutaneous coronary intervention (PCI) is the treatment of choice for acute ST-segment elevation myocardial infarction. In this study, PCI that was “facilitated” by pretreatment with reteplase plus abciximab or abciximab alone did not improve clinical outcomes and increased bleeding, calling into question the use of facilitated PCI for the treatment of acute myocardial infarction.
PCI that was “facilitated” by pretreatment with reteplase plus abciximab or abciximab alone did not improve clinical outcomes and increased bleeding, calling into question the use of facilitated PCI for the treatment of acute myocardial infarction.
Effective and rapid reperfusion is the most important goal in the treatment of patients with acute ST-segment elevation myocardial infarction.¹,² When feasible and when performed in a timely and expert fashion, primary percutaneous coronary intervention (PCI) is the preferred strategy for reperfusion in the treatment of ST-segment elevation myocardial infarction, because it has been shown to produce superior clinical outcomes as compared with fibrinolytic therapy.³–¹³ Primary PCI has not, however, become the treatment of choice in many locales because of logistical difficulties, including the inability to offer this treatment strategy in a timely fashion. The time to treatment . . .

View all citing articles on Scopus

View full text

ST-segment resolution 60 minutes after combination treatment of abciximab with reteplase or reteplase alone for acute myocardial infarction (30-day mortality results from the resolution of ST-segment after reperfusion therapy substudy)

Section snippets

Study population

Study population

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

J Electrocardiol

Am J Cardiol

Am J Cardiol

Lancet

Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial

Lancet